1/9. carbamyl phosphate synthetase 1 deficiency: a destructive encephalopathy.carbamyl phosphate synthetase I is a urea cycle enzyme. Severe deficiency of carbamyl phosphate synthetase I presents in the neonatal period as hyperammonemic encephalopathy with altered consciousness and occasional seizures after feeding begins. Episodes of altered consciousness with or without seizures and focal neurologic deficits are seen later with patients of partial carbamyl phosphate synthetase I deficiency. Fatal cerebral edema with brain herniation may develop on occasion. Three patients presenting with carbamyl phosphate synthetase I deficiency are reported with neuroimaging and pathologic findings illustrating the destructive encephalopathy with acute cerebral edema, followed by diffuse cerebral atrophy and occasional cystic encephalomalacia. The deterioration in carbamyl phosphate synthetase I deficiency occurs during the hyperammonemic crises. This deficiency may be difficult to treat despite the current advances in treatment strategies, especially in neonatal-onset patients with low carbamyl phosphate synthetase I activity.- - - - - - - - - - ranking = 1keywords = cycle (Clic here for more details about this article) |
2/9. ammonia detoxification by continuous venovenous haemofiltration in an infant with urea cycle defect.We report the case of a newborn baby with carbamoyl phosphate synthetase deficiency. He presented at 2 weeks of life, deteriorating to a state of hyperammonaemic coma and respiratory failure. Rapid detoxification was successfully achieved by continuous venovenous haemofiltration while a definitive diagnosis and treatment were determined. The ammonia clearance achieved by continuous venovenous haemofiltration was greater than 20 mL/min/m(2), which is superior to that achieved by peritoneal dialysis and arteriovenous haemofiltration in this age-group.- - - - - - - - - - ranking = 4keywords = cycle (Clic here for more details about this article) |
3/9. brain MR imaging in neonatal hyperammonemic encephalopathy resulting from proximal urea cycle disorders.We present brain MR images in three patients with neonatal-onset hyperammonemic encephalopathy resulting from urea-cycle disorders (two sisters with deficiency of the carbamyl phosphate synthetase I reaction step and one boy with an ornithine transcarbamylase deficiency). MR imaging revealed almost identical findings of injury to the bilateral lentiform nuclei and the deep sulci of the insular and perirolandic regions; to our knowledge, this pattern has not been previously reported. We hypothesize that these lesions presumably reflect the distribution of brain injury due to hypoperfusion secondary to hyperammonemia and hyperglutaminemia in the neonatal period.- - - - - - - - - - ranking = 5keywords = cycle (Clic here for more details about this article) |
4/9. Interstitial deletion of chromosome 2q32-34 associated with multiple congenital anomalies and a urea cycle defect (CPS I deficiency).A de novo deletion of the long arm of chromosome 2 at 2q31-33 was observed in the fetal amniocyte G-banded karyotype performed because of possible multiple malformations identified by ultrasound at 23 weeks gestation. Two days after the uneventful term delivery of a 2.45 kg male, the neonate experienced cardiopulmonary decompensation and biochemical changes compatible with carbamoyl phosphate synthetase I (CPS I) deficiency (elevated ammonia with a peak of 948 micromol/L, deficiency of citrulline, and no increase in orotic acid). The child died on day 3 of life. Physical anomalies confirmed at autopsy included double superior vena cava, ectopic adrenal tissue, and metatarsus adductus. The autopsy also revealed histologic evidence consistent with CPS deficiency, most notably microvesicular steatosis of the liver and Alzheimer's Type II changes with hypertrophic astrocytes in the basal ganglia. A postnatal lymphocyte karyotype confirmed the chromosome 2q31-33 deletion. Enzyme analysis on postmortem liver tissue confirmed the diagnosis of CPS deficiency. CPS I is reported to be mapped to 2q35 by NCBI (http://www.ncbi.nlm.nih.gov/mapview/) and 2q34 by ENSEMBL (http://www.ensembl.org/). The UCSC Human genome Browser July 2003 assembly also places the gene at 2q34 (http://genome.UCSC.edu/). fluorescence in situ hybridization (FISH) analysis with a BAC clone (RP11-349G4) of CPS I demonstrated that one copy of the gene was deleted in this infant. Using additional probes corresponding to the bands in the region of deletion, we identified the deleted region as 2q32-2q34. Our observations support the CPS I map position (ENSEMBL, UCSC) at 2q34. Additionally, potential conditions associated with deletions narrowly defined by standard cytogenetic techniques merit consideration in prenatal counseling. As demonstrated here, deletions may not only result in malformations and mental retardation but also increase the likelihood of revealing mutated genes located in the undeleted region of the homologous chromosome.- - - - - - - - - - ranking = 4keywords = cycle (Clic here for more details about this article) |
5/9. Developmental outcomes with early orthotopic liver transplantation for infants with neonatal-onset urea cycle defects and a female patient with late-onset ornithine transcarbamylase deficiency.urea cycle defects (UCDs) typically present with hyperammonemia, the duration and peak levels of which are directly related to the neurologic outcome. liver transplantation can cure the underlying defect for some conditions, but the preexisting neurologic status is a major factor in the final outcome. Multicenter data indicate that most of the children who receive transplants remain significantly neurologically impaired. We wanted to determine whether aggressive metabolic management of ammonia levels after early referral/transfer to a metabolism center and early liver transplantation would result in better neurologic outcomes. We report on 5 children with UCDs, ie, 2 male patients with X-linked ornithine transcarbamylase deficiency and 2 male patients with carbamoyl phosphate synthase deficiency, all of whom had neonatal presentations and underwent orthotopic liver transplantation before 1 year of age, and 1 female patient with partial X-linked ornithine transcarbamylase deficiency that was intractable to medical therapy, who underwent transplantation at 35 months of age. Developmental testing with the Griffiths scale was performed on 3 occasions each, 12 months apart, up to 45 months after transplantation. Full-scale indices for 3 children who underwent early transplantation showed average developmental quotients of 67. All 5 children had metabolic cures. There were no deaths (30-month survival rate: 100%). One child is currently listed for repeat transplantation because of bile duct stenosis and cirrhosis. We conclude that early liver transplantation and aggressive metabolic management improve early neurologic outcomes for children with UCDs, but longer follow-up monitoring is needed.- - - - - - - - - - ranking = 5keywords = cycle (Clic here for more details about this article) |
6/9. brain glutamine by MRS in a patient with urea cycle disorder and coma.In patients who undergo metabolic decompensation from urea cycle disorders, cerebrospinal fluid glutamine level may be a better marker of cerebral dysfunction than blood ammonia or glutamine levels. However, obtaining cerebrospinal fluid by lumbar puncture carries risk in these acutely ill patients with cerebral edema. Using magnetic resonance single voxel spectroscopy as an alternative to cerebrospinal fluid analysis, elevated brain glutamine/glutamate complex levels were detected in a patient with carbamyl phosphate synthetase deficiency, who had been comatose for many days after normalization of blood ammonia and improvement in blood glutamine levels. brain glutamine by single voxel spectroscopy decreased toward normal with neurologic recovery. We conclude that brain glutamine may be a better marker than serum ammonia for the management of urea cycle disorders, particularly in patients with prolonged mental status changes.- - - - - - - - - - ranking = 6keywords = cycle (Clic here for more details about this article) |
7/9. Unmasked adult-onset urea cycle disorders in the critical care setting.Most often, urea cycle disorders have been described as acute onset hyperammonemia in the newborn period; however, there is a growing awareness that urea cycle disorders can present at almost any age, frequently in the critical care setting. This article presents three cases of adult-onset hyperammonemia caused by inherited defects in nitrogen processing in the urea cycle, and reviews the diagnosis, management, and pathophysiology of adult-onset urea cycle disorders. Individuals who have milder molecular urea cycle defects can lead a relatively normal life until a severe environmental stress triggers a hyperammonemic crisis. Comorbid conditions such as physical trauma often delay the diagnosis of the urea cycle defect. Prompt recognition and treatment are essential in determining the outcome of these patients.- - - - - - - - - - ranking = 10keywords = cycle (Clic here for more details about this article) |
8/9. genetic counseling issues in urea cycle disorders.The goal of counseling families that have a urea cycle disorder (UCD) is to facilitate the process of scientific understanding, emotional acceptance, and decision-making in a nondirective way. A proper understanding of the genes involved, inheritance patterns, available testing, and complicating factors is critical to serving the families' needs. This article summarizes the needed information, in particular describing the complexities of prenatal testing and counseling issues for each UCD. Included case histories illustrate the genetic counseling process and the decision-making scenarios for two families.- - - - - - - - - - ranking = 5keywords = cycle (Clic here for more details about this article) |
9/9. carbamyl phosphate synthase deficiency: diagnosed during pregnancy in a 41-year-old.carbamyl phosphate synthase deficiency (CPS) is a rare urea cycle defect. We present a case of a 41-year-old woman diagnosed with CPS deficiency during pregnancy. She is the oldest CPS-deficient patient, at diagnosis, reported to date and the first to be diagnosed during pregnancy. This case highlights the need for consideration of inborn errors of metabolism in adults presenting with unusual neurological and psychiatric conditions.- - - - - - - - - - ranking = 1keywords = cycle (Clic here for more details about this article) |